Functional reconstitution of a heteromeric cyclic nucleotide-gated channel of Caenorhabditis elegans in cultured cells

Brain Res. 1999 Mar 6;821(1):160-8. doi: 10.1016/s0006-8993(99)01111-7.

Abstract

The tax-4 and tax-2 genes of Caenorhabditis elegans are essential for normal olfaction, gustation, and thermosensation, suggesting that they have a role in sensory transduction. The predicted products of these genes are similar to the cyclic nucleotide-gated (CNG) channel subunits used in vertebrate vision and olfaction: TAX-4 is highly related to those alpha subunits, while TAX-2 is most closely related to the beta subunits of the rod phototransduction channels. TAX-4 has previously been shown to form a highly sensitive cGMP-gated channel when expressed in human HEK293 cells. Here we show that TAX-4 and TAX-2 form a heteromeric channel when expressed in HEK293 cells, but TAX-2 does not form a channel on its own. Since these genes are expressed in the same neurons, most of the native channels in C. elegans are likely to be hetero-oligomers of TAX-4 and TAX-2 subunits, with TAX-4 as the alpha subunit and TAX-2 acting as a modifying beta subunit. The heteromeric TAX-4/TAX-2 channel is 25-fold less sensitive to cGMP than the TAX-4 channel, but it remains highly selective for cGMP over cAMP. The heteromeric channel and the TAX-4 homomeric channel differ in their blockage by divalent cations and in their single channel properties. These results suggest that cGMP is used as the second messenger during sensory signal transduction in C. elegans, and that distinct roles for alpha and beta subunits of CNG channels are conserved in vertebrate and invertebrate signal transduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins*
  • Calcium / pharmacokinetics
  • Cells, Cultured
  • Cyclic AMP / physiology
  • Cyclic GMP / physiology
  • Genes, Helminth
  • Helminth Proteins / genetics
  • Humans
  • Ion Channel Gating
  • Ion Channels / genetics
  • Permeability
  • Second Messenger Systems / physiology
  • Smell / physiology
  • Vision, Ocular / physiology

Substances

  • Caenorhabditis elegans Proteins
  • Helminth Proteins
  • Ion Channels
  • tax-2 protein, C elegans
  • tax-4 protein, C elegans
  • Cyclic AMP
  • Cyclic GMP
  • Calcium